Diabetes,
Journal Year:
2020,
Volume and Issue:
69(3), P. 279 - 290
Published: Feb. 13, 2020
Paraphrasing
the
Swiss
physician
and
father
of
toxicology
Paracelsus
(1493-1541)
on
chemical
agents
used
as
therapeutics,
"the
dose
makes
poison,"
it
is
now
realized
that
this
aptly
applies
to
calorigenic
nutrients.
The
case
here
pancreatic
islet
β-cell
presented
with
excessive
levels
nutrients
such
glucose,
lipids,
amino
acids.
short-term
effects
these
exert
are
enhanced
insulin
biosynthesis
secretion
changes
in
glucose
sensitivity.
However,
chronic
fuel
surfeit
triggers
additional
compensatory
adaptive
mechanisms
by
β-cells
cope
increased
demand
or
protect
itself.
When
fail,
toxicity
due
nutrient
surplus
ensues,
leading
dysfunction,
dedifferentiation,
apoptosis.
terms
glucotoxicity,
lipotoxicity,
glucolipotoxicity
have
been
widely
used,
but
there
some
confusion
what
they
mean
precisely
which
most
appropriate
for
a
given
situation.
Here
we
address
gluco-,
lipo-,
glucolipo-toxicities
assessing
evidence
both
against
each
them.
We
also
discuss
potential
defend
view
many
identified
"toxic"
excess,
may
include
acids,
fact
beneficial
processes.
In
addition,
candidate
fuel-excess
detoxification
pathways
evaluated.
Finally,
propose
more
general
term
should
be
vivo
situation
overweight-associated
type
2
diabetes
reflecting
toxic
processes
mixed
excess:
"nutrient-induced
metabolic
stress"
or,
brief,
"nutri-stress."
Organs-on-chips
(OoCs)
are
systems
containing
engineered
or
natural
miniature
tissues
grown
inside
microfluidic
chips.
To
better
mimic
human
physiology,
the
chips
designed
to
control
cell
microenvironments
and
maintain
tissue-specific
functions.
Combining
advances
in
tissue
engineering
microfabrication,
OoCs
have
gained
interest
as
a
next-generation
experimental
platform
investigate
pathophysiology
effect
of
therapeutics
body.
There
many
examples
there
applications,
making
it
difficult
for
new
researchers
understand
what
makes
one
OoC
more
suited
an
application
than
another.
This
Primer
is
intended
give
introduction
aspects
that
need
be
considered
when
developing
application-specific
OoC.
The
covers
guiding
principles
considerations
design,
fabricate
operate
OoC,
well
subsequent
assaying
techniques
extract
biological
information
from
devices.
Alongside
this
discussion
current
future
applications
technology,
inform
design
operational
decisions
during
implementation
systems.
with
aim
mimicking
physiology
range
biomedical
therapeutic
applications.
Leung,
de
Haan
et
al.
report
practical
tips
organ-on-a-chip
Physiological Reviews,
Journal Year:
2021,
Volume and Issue:
101(4), P. 1745 - 1807
Published: May 5, 2021
The
prevalence
of
heart
failure
is
on
the
rise
and
imposes
a
major
health
threat,
in
part,
due
to
rapidly
increased
overweight
obesity.
To
this
point,
epidemiological,
clinical,
experimental
evidence
supports
existence
unique
disease
entity
termed
"obesity
cardiomyopathy,"
which
develops
independent
hypertension,
coronary
disease,
other
diseases.
Our
contemporary
review
evaluates
for
pathological
condition,
examines
putative
responsible
mechanisms,
discusses
therapeutic
options
disorder.
Clinical
findings
have
consolidated
presence
left
ventricular
dysfunction
Experimental
investigations
uncovered
pathophysiological
changes
myocardial
structure
function
genetically
predisposed
diet-induced
Indeed,
consolidates
wide
array
cellular
molecular
mechanisms
underlying
etiology
obesity
cardiomyopathy
including
adipose
tissue
dysfunction,
systemic
inflammation,
metabolic
disturbances
(insulin
resistance,
abnormal
glucose
transport,
spillover
free
fatty
acids,
lipotoxicity,
amino
acid
derangement),
altered
intracellular
especially
mitochondrial
Ca2+
homeostasis,
oxidative
stress,
autophagy/mitophagy
defect,
fibrosis,
dampened
flow
reserve,
microvascular
(microangiopathy),
endothelial
impairment.
Given
important
role
risk
failure,
that
with
preserved
systolic
recent
rises
COVID-19-associated
cardiovascular
mortality,
should
provide
compelling
cardiomyopathy,
various
comorbid
conditions,
offer
new
insights
into
potential
approaches
(pharmacological
lifestyle
modification)
clinical
management
cardiomyopathy.
Frontiers in Endocrinology,
Journal Year:
2023,
Volume and Issue:
14
Published: March 28, 2023
Insulin
resistance
(IR)
plays
a
crucial
role
in
the
development
and
progression
of
metabolism-related
diseases
such
as
diabetes,
hypertension,
tumors,
nonalcoholic
fatty
liver
disease,
provides
basis
for
common
understanding
these
chronic
diseases.
In
this
study,
we
provide
systematic
review
causes,
mechanisms,
treatments
IR.
The
pathogenesis
IR
depends
on
genetics,
obesity,
age,
drug
effects.
Mechanistically,
any
factor
leading
to
abnormalities
insulin
signaling
pathway
leads
host,
including
receptor
abnormalities,
disturbances
internal
environment
(regarding
inflammation,
hypoxia,
lipotoxicity,
immunity),
metabolic
function
organelles,
other
abnormalities.
available
therapeutic
strategies
are
mainly
exercise
dietary
habit
improvement,
chemotherapy
based
biguanides
glucagon-like
peptide-1,
traditional
Chinese
medicine
(e.g.,
herbs
acupuncture)
can
also
be
helpful.
Based
current
there
still
some
vacancies
follow
up
consider,
is
need
define
more
precise
biomarkers
different
lifestyle
interventions,
explore
natural
or
synthetic
drugs
targeting
treatment.
This
could
enable
treatment
patients
with
multiple
combined
diseases,
aim
treating
disease
holistically
reduce
healthcare
expenditures
improve
quality
life
extent.
Journal of Hepatology,
Journal Year:
2022,
Volume and Issue:
78(2), P. 415 - 429
Published: Oct. 7, 2022
Fatty
liver
diseases
can
result
from
common
metabolic
diseases,
as
well
xenobiotic
exposure
and
excessive
alcohol
use,
all
of
which
have
been
shown
to
exert
toxic
effects
on
hepatic
mitochondrial
functionality
dynamics.
Invasive
or
complex
methodology
limits
large-scale
investigations
mitochondria
in
human
livers.
Nevertheless,
abnormal
function,
such
impaired
fatty
acid
oxidation
oxidative
phosphorylation,
drives
stress
has
identified
an
important
feature
steatohepatitis.
On
the
other
hand,
be
flexible
adapt
ambient
condition
prevent
triglyceride
lipotoxin
accumulation
obesity.
Experience
studies
xenobiotics
provided
insights
into
regulation
mitochondria.
Increasing
awareness
joint
presence
disease-related
(lipotoxic)
alcohol-related
further
highlights
need
better
understand
their
mutual
interaction
potentiation
disease
progression.
Recent
clinical
assessed
diets
bariatric
surgery
mitochondria,
are
also
evolving
interesting
therapeutic
target
non-alcoholic
disease.
This
review
summarises
current
knowledge
with
a
focus
linked
obesity,
type
2
diabetes
xenobiotics.
Cell Death and Disease,
Journal Year:
2020,
Volume and Issue:
11(10)
Published: Oct. 24, 2020
Abstract
Obesity
has
been
recognized
as
a
major
risk
factor
for
chronic
kidney
disease,
but
the
underlying
mechanism
remains
elusive.
Here,
we
investigated
whereby
long-term
high-fat
diet
(HFD)
feeding
induces
renal
injury
in
mice.
The
C57BL/6
mice
fed
HFD
16
weeks
developed
obesity,
diabetes,
and
dysfunction
manifested
by
albuminuria
blood
accumulation
of
BUN
creatinine.
HFD-fed
showed
marked
glomerular
tubular
injuries,
including
prominent
defects
filtration
barrier
increased
cell
apoptosis.
Mechanistically,
markedly
triglyceride
cholesterol
contents
activated
lipogenic
pathways
synthesis.
also
oxidative
stress
induced
mitochondrial
fission
cells,
thereby
activating
pro-apoptotic
pathway.
In
HK-2
mesangial
cultures,
high
glucose,
fatty
acid,
TNF-α
combination
was
able
to
activate
pathways,
increase
stress,
promote
fission,
pathway,
all
which
could
be
attenuated
an
inhibitor
that
depleted
reactive
oxygen
species.
Taken
together,
these
observations
suggest
causes
at
least
part
result
tissue
lipid
accumulation,
dysfunction,
excess
programmed
death.